The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp3)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.
A transition metal‐free coupling reaction of benzylboronic esters and alkyl halides has been developed. Both alkyl bromides and alkyl iodides were found to be competent substrates with the nucleophilic boronate intermediate generated from the combination of benzylboronic ester and an alkyllithium. Good chemoselectivity was observed for the reaction with the alkyl bromide in substrates with a second electrophile present. Both secondary and tertiary benzylboronic esters were effective nucleophiles in the reaction with primary alkyl halides. Mechanistic observations are consistent with a radical mechanism.
more » « less- NSF-PAR ID:
- 10238402
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- European Journal of Organic Chemistry
- Volume:
- 2021
- Issue:
- 19
- ISSN:
- 1434-193X
- Page Range / eLocation ID:
- p. 2782-2784
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
Abstract The Mizoroki–Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3)−H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β‐, γ‐, and δ‐C(sp3)−H sites. The use of an easily installed/removed Si‐based auxiliary enables selective I‐atom/radical translocation events at remote C−H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible‐light‐mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.
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Abstract Diverse alkenylboronic acids react smoothly with various
sp 3‐carbon electrophiles such as unactivated alkyl triflates in the presence of mild bases such as K3PO4. The reaction protocol is very mild and thereby enables high functional group tolerance. This transition metal‐free condition is orthogonal towards the classic transition metal catalyzed Suzuki coupling.magnified image -
Abstract Electrochemical approaches to form C(sp2)−C(sp3) bonds have focused on coupling C(sp3) electrophiles that form stabilized carbon‐centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp3) coupling partners owing to their availability and cost‐effectiveness, their tendency to undergo radical‐radical homocoupling makes them challenging substrates for electroreductive cross‐coupling. Herein, we disclose a metal‐free regioselective cross‐coupling of 1,4‐dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4‐dicyanobenzene radical anions, leading to negligible homocoupling and high cross‐selectivity to form 1,4‐alkyl cyanobenzenes. The cross‐coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp3) precursors.
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Abstract Electrochemical approaches to form C(sp2)−C(sp3) bonds have focused on coupling C(sp3) electrophiles that form stabilized carbon‐centered radicals upon reduction or oxidation. Whereas alkyl bromides are desirable C(sp3) coupling partners owing to their availability and cost‐effectiveness, their tendency to undergo radical‐radical homocoupling makes them challenging substrates for electroreductive cross‐coupling. Herein, we disclose a metal‐free regioselective cross‐coupling of 1,4‐dicyanobenzene, a useful precursor to aromatic nitriles, and alkyl bromides. Alkyl bromide reduction is mediated directly by 1,4‐dicyanobenzene radical anions, leading to negligible homocoupling and high cross‐selectivity to form 1,4‐alkyl cyanobenzenes. The cross‐coupling scheme is compatible with oxidatively sensitive and acidic functional groups such as amines and alcohols, which have proven difficult to incorporate in alternative electrochemical approaches using carboxylic acids as C(sp3) precursors.